IPC분류정보
국가/구분 |
United States(US) Patent
등록
|
국제특허분류(IPC7판) |
|
출원번호 |
US-0485116
(2002-08-06)
|
국제출원번호 |
PCT/IL02/000643
(2002-08-06)
|
§371/§102 date |
20040205
(20040205)
|
국제공개번호 |
WO03/014795
(2003-02-20)
|
발명자
/ 주소 |
- Kaplan,Eran
- Freiberger,Avner
|
출원인 / 주소 |
|
인용정보 |
피인용 횟수 :
15 인용 특허 :
2 |
초록
▼
An imaging apparatus with an autofocus mechanism for obtaining focused images. The apparatus comprises: an objective lens, a focus controller for altering a distance between the objective lens and a sample, an object finder for finding objects of interest within the sample, for example cells, and a
An imaging apparatus with an autofocus mechanism for obtaining focused images. The apparatus comprises: an objective lens, a focus controller for altering a distance between the objective lens and a sample, an object finder for finding objects of interest within the sample, for example cells, and a light intensity measurement unit which measures light intensity levels of the thus identified objects of interest. The focus control alters the sample-objective distance to maximize the light intensity levels being measured, thereby to arrive at a focus position. Objects of interest may be identified by filtering out large objects and optionally by masking out background regions. The apparatus is useful for microscopy and particularly for fluorescent imaging in which light levels are low and noise is often high.
대표청구항
▼
We claim: 1. An imaging apparatus for taking images of samples, the apparatus comprising: an objective lens, a focus controller for altering a distance between said objective lens and said sample, an object finder for finding objects of interest within said sample, a light intensity measurement uni
We claim: 1. An imaging apparatus for taking images of samples, the apparatus comprising: an objective lens, a focus controller for altering a distance between said objective lens and said sample, an object finder for finding objects of interest within said sample, a light intensity measurement unit, associated with said focus controller, arranged to calculate the sum of light intensity levels, gathered through said objective lens, of said objects of interest, said apparatus being operable to alter said distance to maximize said calculated sum of light intensity levels, thereby to find a focus position. 2. The imaging apparatus of claim 1, wherein said focus controller is controllable to stepwise alter said focus through a series of distances to allow said light intensity measurement unit to measure said light intensity at each of said focus distances, therefrom to select one of said focus distances giving maximum intensity as said focus position. 3. The imaging apparatus of claim 1, being comprised within a camera. 4. The imaging apparatus of claim 1, where said sample is a fluorescent sample. 5. The imaging apparatus of claim 1, wherein said object finder comprises a small object filter for filtering to include only small objects of said sample. 6. The imaging apparatus of claim 4, wherein said object finder comprises a bright object filter for filtering out objects fluorescing above a predetermined fluorescing threshold. 7. The fluorescent imaging apparatus of claim 4, wherein said object finder comprises a background filter for filtering out a background color. 8. The fluorescent imaging apparatus of claim 6, wherein said object finder comprises a background filter for filtering out a background color. 9. The imaging apparatus of claim 1, further comprising a filter for filtering out objects fluorescing above a predetermined fluorescing threshold. 10. The imaging apparatus of claim 5, wherein said small object filter is operable to filter out regions not being objects occupying less space than substantially 500 pixels of an image. 11. The imaging apparatus of claim 3, wherein said light intensity measurement unit is operable to compute an average intensity over an image taken of said sample using at least a first of said focusing distances. 12. The imaging apparatus of claim 11, wherein said light intensity measurement unit is further operable to compute a standard deviation of said intensity over said image. 13. The imaging apparatus of claim 12, further comprising a thresholder associated with said light intensity measurement unit for using said average intensity and said standard deviation to compute an image threshold for thresholding pixels of said image. 14. The imaging apparatus of claim 13, wherein said threshold is the average intensity plus a predetermined image constant times the standard deviation. 15. The imaging apparatus of claim 13, wherein said thresholder is operable to compute a focusing threshold in addition to said image threshold. 16. The imaging apparatus of claim 15, wherein said focusing threshold is the average intensity plus a predetermined focusing constant times the standard deviation. 17. The imaging apparatus of claim 5, wherein said small object filter is operable to filter for said small objects by forming a mask by setting to zero any pixel that is outside of an object being smaller than a predetermined blob size. 18. The imaging apparatus of claim 17, further comprising a thresholder, operable to threshold an image using a brightness threshold. 19. The imaging apparatus of claim 18, wherein said thresholder is operable to threshold for brightness separately for color bands of said image. 20. The imaging apparatus of claim 19, wherein said thresholder is operable to threshold for brightness separately for color bands of said image such as to filter out a color associated with an image background, thereby to provide a background filter. 21. The imaging apparatus of claim 17, further comprising combination logic for ANDing said thresholded image with said mask. 22. The imaging apparatus of claim 20, further comprising combination logic for ANDing said thresholded image with said mask, thereby to form an image comprising delineated objects of interest. 23. The imaging apparatus of claim 21, further comprising a noise remover operable to set to zero each pixel of said image lacking at least one non-zero pixel as a neighbor. 24. The imaging apparatus of claim 23, wherein said noise remover comprises a rank filter. 25. The imaging apparatus of claim 24, further comprising a focus scorer for computing a focus score to an image, the focus scorer comprising a summator for summing over substantially each pixel in the image the difference, raised to the power of a predetermined constant, between the pixel intensity level and the average intensity level for the image. 26. The imaging apparatus of claim 25, wherein said predetermined constant is a positive number. 27. The imaging apparatus of claim 26, wherein said predetermined constant is substantially 2. 28. The imaging apparatus of claim 27, further comprising a comparator associated with said focus scorer, for determining which of said images gives a maximum score, thereby to select an optical focus position. 29. The imaging apparatus of claim 1, comprising an exposure timer having a predetermined exposure time for producing focusing images and a predetermined exposure time for producing viewing images and wherein said predetermined exposure time for producing focusing images is shorter than said predetermined exposure time for producing viewing images. 30. The imaging apparatus of claim 29, wherein a ratio between said exposure times is substantially between a third and a fortieth. 31. The imaging apparatus of claim 29, wherein a ratio between said exposure times is substantially between a tenth and a fifth. 32. The imaging apparatus of claim 29, wherein a ratio between said exposure times is calculable by taking substantially the square root of a ratio between a typical image SNR and an empirically determined SNR for a given focused image. 33. The imaging apparatus of claim 29, said exposure timer being set to increase said predetermined exposure time for producing focusing images in the event of a determination of a focusing failure. 34. The imaging apparatus of claim 25, comprising a comparator for determining a difference between focus scores of successive images, said apparatus being operable to reduce exposure time when said difference is above a predetermined level. 35. The imaging apparatus of claim 34, further comprising a focus score adjuster operable to adjust respective focus scores of focusing images to compensate for said reductions in said exposure time. 36. The imaging apparatus of claim 1, further comprising pixel binning functionality to increase a signal to noise ratio of said images. 37. The imaging apparatus of claim 1, comprising a light intensity detector connected to a servo-unit for altering said distance, said servo-unit being controllable to alter said distance to maximize light intensity as detected by said detector. 38. The imaging apparatus of claim 37, further comprising a large object detector for inhibiting action of said servo-unit when the presence of a large object is detected. 39. The imaging apparatus of claim 37, comprising a low magnification pre-scanner for determining whether large objects are present in the sample, and inhibiting the operation of said server unit in the presence of said large objects. 40. The imaging apparatus of claim 1, said light intensity detection unit comprising a multi-pixel array. 41. A method of image focusing comprising: illuminating a sample, collecting light from said sample via an objective lens, therefrom to form an image, thresholding said image against a threshold brightness level, identifying objects within said image of brightness higher than said threshold brightness level, filtering small objects of interest within said bright objects, creating an image mask including only said filtered small objects of interest, summing subsequent image intensities of each of said small objects substantially corresponding to objects of said mask, to calculate a focusing score altering a distance between said objective lens and said sample and repeatedly calculating said focusing score for each image taken after said distance has been altered: selecting a focusing distance substantially corresponding to that of an image having a maximum calculated focusing score. 42. A method of producing a focused image comprising: taking a series of images, over said series filtering for small objects, over said series thresholding said images against a threshold brightness level, summing intensities of each filtered and thresholded image to form a focusing score for each image, and, using said summed intensities, selecting a focusing distance substantially corresponding to that of an image having a maximum focusing score. 43. An autofocus device for use in imaging, the device comprising: an object identifier for identifying regions of interest within an unfocused image of said sample, and a light intensity measurement unit arranged to measure light intensity levels of said objects of interest and summate said measured light intensity, and wherein said autofocus device is operable to alter said distance to maximize said summated measured light intensity levels of said objects of interest. 44. The autofocus device of claim 43, wherein said altering of said distance comprises altering said distance stepwise to measure said light intensity at each of said steps and to select a one of said steps giving maximum intensity as a focus distance. 45. The autofocus device of claim 43, wherein said object identifier comprises a small object filter for filtering for small objects of said sample. 46. The autofocus device of claim 43, wherein said small object filter comprises a blob analyzer having a predetermined blob size, for recognizing objects that do not exceed said predetermined blob size. 47. The autofocus device of claim 46, wherein said predetermined blob size is substantially 500 pixels. 48. The autofocus device of claim 44, wherein said light intensity measurement unit is operable to compute an average intensity over an image taken of said sample using at least a first of said focus steps. 49. The autofocus device of claim 48, said light intensity measurement unit further being operable to compute a standard deviation of said intensity over said image. 50. The autofocus device of claim 49, further comprising a thresholder associated with said light intensity measurement unit for using said average intensity and said standard deviation to compute an image intensity threshold for thresholding pixels of said image. 51. The autofocus device of claim 50, wherein said image intensity threshold is the average intensity plus a predetermined image constant times the standard deviation. 52. The autofocus device of claim 50, wherein said thresholder is operable to compute a focusing threshold in addition to said image threshold. 53. The autofocus device of claim 52, wherein said focusing threshold is the average intensity plus a predetermined focusing constant times the standard deviation. 54. The autofocus device of claim 45, wherein said small object filter is operable to form a mask from an image taken at a predetermined focus position by setting to zero any pixel not being part of an object that is smaller than a predetermined large object threshold. 55. The autofocus device of claim 54, further comprising combination logic for ANDing said thresholded image with said mask, thereby to form an image delineating said objects of interest. 56. The autofocus device of claim 55, further comprising a noise remover operable to set to zero each pixel of said image lacking at least one non-zero pixel as a neighbor. 57. The autofocus device of claim 56, wherein said noise remover comprises a rank filter. 58. The autofocus device of claim 57, further comprising a focus scorer for computing a focus score to an image, the focus scorer comprising a summator for summing over substantially each pixel in the image the difference, raised to the power of a predetermined constant, between the pixel intensity level and the average intensity level for the image. 59. The autofocus device of claim 58, wherein said predetermined constant is a positive number. 60. The autofocus device of claim 59, wherein said predetermined constant is substantially 2. 61. The autofocus device of claim 60, further comprising a comparator associated with said focus scorer, for determining which of said images gives a maximum score, thereby to alter said distance to a distance corresponding to said position to focus said sample. 62. The autofocus device of claim 43, comprising an exposure timer having a predetermined exposure time for producing focusing images and a predetermined exposure time for producing viewing images and wherein said predetermined exposure time for producing focusing images is shorter than said predetermined exposure time for producing viewing images. 63. The autofocus device of claim 62, wherein a ratio between said exposure times is substantially between a fifth and a fortieth. 64. The autofocus device of claim 62, wherein a ratio between said exposure times is substantially between a tenth and a twentieth. 65. The autofocus device of claim 62, wherein a ratio between said exposure times is obtainable by taking the square root of a ratio between a typical image SNR and an empirically determined SNR for a given focused image. 66. The autofocus device of claim 62, said exposure timer being set to increase said predetermined exposure time for producing focusing images in the event of a determination of a focusing failure. 67. The autofocus device of claim 58, comprising a comparator for determining a difference between focus scores of successive images, said apparatus being operable to reduce exposure time when said difference is above a predetermined level. 68. The autofocus device of claim 67, further comprising a focus score adjuster operable to adjust respective focus scores of focusing images to compensate for said reductions in said exposure time. 69. The autofocus device of claim 43, further comprising pixel binning functionality to increase a signal to noise ratio of said images. 70. The autofocus device of claim 43, comprising a low magnification pre-scanner for determining whether large objects are present in a sample to be imaged, and inhibiting the operation of said server unit in the presence of said large objects. 71. The autofocus device of claim 43, wherein said light intensity detection unit comprises a multi-pixel array. 72. An autofocus device for a fluorescence imaging microscope, the device comprising an image filter for filtering an image to delineate objects of interest and a light intensity measurement unit associated with a focusing mechanism for focusing by altering a focus distance to maximize a calculated sum of measured light intensity of said filtered image. 73. The autofocus device of claim 72, being operable to carry out said focusing using image data gathering at a lower data level than a data level needed for imaging.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.